Background The threat of drug resistant fungal infections poses an urgent and increasing global health problem in the absence of wholly effective antifungal therapeutics. Resistance to available classes of antifungals has been reported & with the emergence of multi-drug resistant species such as Candida auris, there has never been a more urgent need for new antifungals. NovaBiotics has developed NP339, a therapeutic antimicrobial peptide active against pathogenic fungi, including, but not exclusively Candida spp. Aspergillus spp. Cryptococcus spp. Scedosporium spp. and mucorales strains. Methods Antimicrobial susceptibility testing with NP339 was carried out against 160 fungi using CLSI M27-A3 for yeast and CLSI M38-A2 for filamentous fungi. The time to kill was determined by exposing fungi to drug/drug candidate for 48h, plating out to determine cfu. Candida spp. and Cryptococcus spp. were passaged over multiple exposures to 0.25x MIC100 NP339 or standard of care antifungals and any change to MIC determined every fifth passage. Results Across all strains analysed, including multi-drug resistant isolates, the median MIC of NP339 against Candida spp., Cryptococcus spp., Exophiala spp., & Scedosporium spp. was 2-4mg/L and mucorales strains & Aspergillus spp had a median of 8mg/L & 16mg/L respectively. NP339 is rapidly fungicidal, resulting in 3 log reduction in cfu within 4h against C. auris. Over the course of 30 exposures to sub-MIC, resistance to NP339 did not develop in Candida spp. or Cryptococcus spp. tested but did to standard of care antifungals as determined by an increase in MIC. Of note, the susceptibility to NP339 of those cells exposed, and more resistant to, standard of care antifungals did not change from 2-4mg/L when reassessed. Conclusion NP339 is a broad spectrum antifungal candidate demonstrating significant potential as a much needed new treatment for invasive fungal infections facilitating rapid fungicidal activity against a broad range of clinically relevant fungi. Candida spp. & Cryptococcus spp. developed no resistance over 30 passages. NP339 is equally active against pathogens resistant to current standard of care antifungals. This data is encouraging as regards NP339’s development as a much needed antifungal that circumvents existing drug resistance and mitigates opportunities for resistance development in the future.
Full conference title:
- ASM Microbe 2nd (2017)